Early-onset non-MuSK nonthymoma |
<40 |
Hyperplasia |
DR3-B8 DR9 (in Asians) |
+ (100%) |
− (100%) |
+ (10%) |
− (100%) |
These patients are more often female. In addition to anti-AChR antibodies, other organ-specific autoantibodies might be present, and patients might be affected by other autoimmune diseases, most commonly autoimmune thyroid disease. Antibodies to non-AChR muscle components are not typically seen in early-onset MG |
Late-onset non-MuSK non-thymoma |
>40 |
Normal/thymic atrophy |
DR2-B7 |
+ (100%) |
− (100%) |
+ (58%) |
+ (14%) |
These patients are more often male and usually have normal thymic histology or thymic atrophy. They can present with ocular or generalized weakness, but typically have a more severe disease course compared with early-onset MG, and spontaneous remissions are rare. The presence of anti-ryanodine receptor antibodies has been associated with more severe, generalized, or predominantly oropharyngeal weakness, and frequent myasthenic crises |
MuSK positive (regardless of onset age) |
<40 (most patients) |
Normal |
DR14-DQ5 |
− (100%) |
+ (100%) |
NA |
NA |
Whereas patients with anti-MuSK antibodies can have presentations similar to anti-AChR-positive MG, they commonly have atypical clinical features, such as selective facial, bulbar, neck, and respiratory muscle weakness and marked muscle atrophy, occasionally with relative sparing of ocular muscles. Respiratory crises are more common than in generalized anti-AChR–positive disease. Weakness can involve muscles that are not usually symptomatic in MG, such as paraspinal and upper esophageal muscles. Enhanced sensitivity, nonresponsiveness, and even clinical worsening in response to anticholinesterase agents have also been reported. Disease onset in patients with anti-MuSK MG tends to be earlier, and patients are predominantly female |
Seronegative (regardless of onset age) |
|
|
|
− (100%) |
− (100%) |
− (100%) |
− (100%) |
Patients with MG who lack both anti-AChR and anti-MuSK antibodies (so-called seronegative MG) are clinically heterogeneous and can have purely ocular, mild generalized, or severe generalized disease. The true prevalence of seronegative MG might be quite low, because some patients might have low-affinity anti-AChR antibodies that are not detected with currently available assays. Not surprisingly, these patients are essentially indistinguishable from patients with anti-AChR–positive MG in terms of clinical features, pharmacological treatment response, and even thymic abnormalities in some cases |
Thymoma (regardless of onset age) |
|
|
|
+ (100%) |
May occur in some patients |
+ (95%) |
+ (70%) |
About 10–15% of patients with MG have a thymic epithelial tumor – a thymoma. Thymoma-associated MG is equally common in men and women and can occur at any age, with peak onset at the age of 50 years2323. Nam T-S, Lee SH, Kim B-C, et al. Clinical characteristics and predictive factors of myastenic crisis after thymectomy. J Clin Neurosci 2011;18:1185-1188.
2424. Soleimani A, Moayyeri A, Akhondzadeh S, et al. Frequency of myasthenic crisis in relation to thymectomy in generalizated myasthenia crisis:a 17 years experience. BMC Neurol 2004;4:12.. Clinical presentations tend to be more severe than in nonthymomatous patients with early-onset MG, commonly with progressive generalized and oropharyngeal weakness. However, long-term prognosis is similar to that of late onset, nonthymomatous MG. With rare exceptions, MG patients with thymoma have high titers of anti-AChR antibodies, and they usually also have antibodies against titin. Additional paraneoplasia-associated antibodies (and their related syndromes) might occur in thymomatous MG, including anti-voltage-gated K+ and Ca2+ channel, anti-Hu (antineuronal nuclear autoantibody 1), antidihy-dropyrimidinase-related protein 5 (formerly anticollapsin response mediator protein 5), and antiglutamic acid decarboxylase antibodies. The presence of autoantibodies to a voltage-gated K+ channel, KCNA4 (formerly Kv1.4), has been recently reported in Japanese patients with severe MG, thymoma, and concomitant myocarditis and/or myositis. In patients with thymoma, surgery (thymothymectomy) often completely and permanently removes the tumor, but symptoms of MG usually persist and require chronic immunotherapy |